DESCRIPTION: (Applicant's Abstract) The broad objective of this proposal is to establish a quantitative algorithmic link between cellular and molecular events involved in reward processing and the behaviors that these events influence. In particular, we will focus on the nature and use of information that midbrain dopamine systems construct and distribute to neural structures throughout the brain. The activity of dopamine neurons of the ventral segmental area and substantia nigra has long been identified with the processing of rewarding stimuli. These neurons send axons to brain structures involved in motivation and goal directed behavior. These same dopamine systems are targets for disruption by disease and by drugs of abuse like heroine and cocaine. In alert primates, experiments show that the outputs of these neurons encode errors between the predictions of future rewards and actual times and magnitudes of future rewards. The prediction errors are apparently encoded as changes in the instantaneous spiking rates: values above baseline mean that the current state is 'better than predicted', values below mean that the current state is 'worse than predicted', and no difference means that 'things are as predicted'. We have developed a computational model of the behavior of midbrain dopamine neurons using a method of adaptive optimizing control called the method of temporal differences. The model is consistent with electrophysiological and behavioral data in monkeys, and also provably executes the appropriate computational function of determining which actions maximize long-term rewards. The long term goal of this project is to provide a computational connection between the action of dopaminergic mechanisms at the molecular and cellular level and the consequences of these mechanisms on behaviors observed in drug addiction. Three approaches will be used to accomplish this long term goal: (1) human behavioral experiments, (2) mathematical analysis, and (3) computer simulations of virtual creatures in complex environments. These three methods will focus on the function of dopaminergic systems in the primate and will be used to probe how normal mechanisms for making decisions in the face of rewards can be disrupted in addiction.